Radiotherapy (RT) is an integral component of the treatment of early stage breast cancer following breast conservation and following mastectomy in high-risk patients. Previous reports have clearly documented, however, the potential for cardiac and pulmonary toxicity secondary to radiation injury, particularly in patients treated comprehensively to the regional nodes. Intensity modulated radiotherapy (IMRT) is a new treatment delivery technique that uses a variable intensity pattern determined with the aid of a computerized optimization algorithm. Preliminary results with IMRT in treatment of the breast only are promising with respect to improved target coverage and sparing of normal tissue. No studies to date, however, have prospectively compared the use of IMRT with the best standard three-dimensional (3-D) planning technique, with respect to cardiac and pulmonary exposure, in patients comprehensively treated to the breast/chest wall and regional nodes. Therefore, the long-term objective of this research will be to compare comprehensive RT delivered using IMRT against the best 3D standard treatment technique (Partially Wide Tangential Fields (PWTF)). Prior to proceeding with this randomized comparison, the IMRT technique that provides the best target dose distributions while adequately sparing the heart and lungs must first be determined. Therefore in this proposal, plans accounting for individual patient set-up uncertainty and ventilatory motion as well as breath hold plans will be developed, optimized, and compared, and the best IMRT plan will be determined using defined metrics. This IMRT plan will subsequently be compared to the present standard PWTF in a randomized trial. Specific Aims: Determine an improved IMRT treatment technique which includes consideration of organ motion and set-up uncertainty by: (1) measuring organ motion and set-up uncertainty in patients undergoing radiotherapy for breast cancer; (2) performing a CT-based planning study comparing PWTF and IMRT plans that compensate for set-up uncertainty and breathing motion to breath hold plans (using Active Breathing Control); (3) selecting the planning technique that is best according to defined target volume, heart, and lung metrics. Study Design: (1) Establish cost functions that drive the optimization to develop the IMRT plan using heart, lung, opposite breast, and spinal cord constraints while maximizing target coverage to the breast/chest wall and nodes. (2) Optimize the best IMRT plan for 20 static cases and compare the static IMRT plan with PWTF using heart and lung metrics. (3) Measure the distribution of set-up errors and motion of target volumes in a cohort of 20 patients. (4) Determine the effect of motion on static IMRT and PWTF dose distributions, and then correct/adjust for motion to determine the best delivery-optimized plan.